Muscle-derived interleukin-6: Lipolytic, anti-inflammatory and immune regulatory effects

Bente Klarlund Pedersen, Adam Steensberg, Pernille Keller, Charlotte Keller, Christian Fischer, Natalie Hiscock, Gerrit Van Hall, Peter Plomgaard, Mark A. Febbraio

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162 Citations (Scopus)


Interleukin-6 (IL-6) is produced locally in working skeletal muscle and can account for the exercise-induced increase in plasma IL-6. The transcription rate for IL-6 in muscle nuclei isolated from muscle biopsies during exercise is very high and is enhanced further when muscle glycogen content is low. Furthermore, cultured human primary muscle cells can increase IL-6 mRNA when incubated with the calcium ionophore ionomycin and it is likely that myocytes produce IL-6 in response to muscle contraction. The biological roles of muscle-derived IL-6 have been investigated in studies in which human recombinant IL-6 was infused in healthy volunteers to mimic closely the IL-6 concentrations observed during prolonged exercise. Using stable isotopes, we have demonstrated that physiological concentrations of IL-6 induce lipolysis. Although we have yet to determine the precise biological action of muscle-derived IL-6, our data support the hypothesis that the role of IL-6 released from contracting muscle during exercise is to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery during exercise. In addition, IL-6 inhibits low-level TNF-α production, and IL-6 produced during exercise probably inhibits TNF-α-induced insulin resistance in peripheral tissues. Hence, IL-6 produced by skeletal muscle during contraction may play an important role in the beneficial health effects of exercise.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Issue number1
Publication statusPublished - 1 Apr 2003
Externally publishedYes


  • Cytokine
  • Exercise
  • Interleukin
  • Metabolism
  • Muscle
  • Physical activity

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